Neurochemical and Anatomical Pathways in the Vertebrate Retina that Mediate Vision Dr. Brecha’s major research interest is concerned with understanding the functional organization of the mammalian retina by elucidating its morphology and neurochemistry. Specific investigations are focused on defining the microcircuitry of the inner retina, evaluating the neurochemical organization and regulation of both its fast (amino acid) and slow (peptide) transmitter systems, and the function of bipolar, amacrine and ganglion cell populations, which are major retinal cell types that play critical roles in the processing of visual information. Recent investigations concerned with peptide-containing cell populations are defining the cellular expression patterns of tachykinin, somatostatin, neuropeptide Y and opiate receptors, and their functional role in modulating bipolar cell responsiveness. Morphological studies have shown that peptide receptor subtypes are selectively expressed by different populations of bipolar, amacrine and ganglion cells. These observations have provided important clues to the organization of the retinal microcircuits mediating different aspects of vision, as well as the sites of action of several previously identified retinal transmitter substances. A new research direction, developed over the past three years has been focused on determining the function of peptides in the retina. The rationale of these studies is to define the cellular actions of peptides found in the retina, which we hypothesize modulate cellular responsiveness, to influence ion channels and other intercellular messenger systems. Initial studies have focused on somatostatin; our findings demonstrate that this peptide inhibits both K+ and Ca2+ ion channels in the axonal terminals of bipolar cells and photoreceptors at low concentrations. Interestingly, these cells prominently express the somatostatin receptor subtype, sst2A suggesting this action is mediated through this receptor. These investigations provide further support for a role of somatostatin in the presynaptic modulation of transmitter release from retinal cells.
Liu Xue, Hirano Arlene A, Sun Xiaoping, Brecha Nicholas C, Barnes Steven Calcium channels in rat horizontal cells regulate feedback inhibition of photoreceptors through an unconventional GABA- and pH-sensitive mechanism The Journal of physiology, 2013; .
Zampighi GA, Schietroma C, Zampighi LM, Woodruff M, Wright EM, Brecha NC Conical tomography of a ribbon synapse: structural evidence for vesicle fusion PLoS One, 2011; 6(3): e16944.
Zampighi Guido A, Schietroma Cataldo, Zampighi Lorenzo M, Woodruff Michael, Wright Ernest M, Brecha Nicholas C Conical tomography of a ribbon synapse: structural evidence for vesicle fusion PloS one, 2011; 6(3): e16944.
Hirano AA, Brandstätter JH, Morgans CW, Brecha NC SNAP25 expression in mammalian retinal horizontal cells J Comp Neurol, 2011; 519(5): 972-88.
Hirano Arlene A, BrandstÃ¤tter Johann Helmut, Morgans Catherine W, Brecha Nicholas C SNAP25 expression in mammalian retinal horizontal cells The Journal of comparative neurology, 2011; 519(5): 972-88.
Guo C, Hirano AA, Stella SL Jr, Bitzer M, Brecha NC Guinea pig horizontal cells express GABA, the GABA-synthesizing enzyme GAD 65, and the GABA vesicular transporter J Comp Neurol, 2010; 518(10): 1674-69.
Guo Chenying, Hirano Arlene A, Stella Salvatore L, Bitzer Michaela, Brecha Nicholas C Guinea pig horizontal cells express GABA, the GABA-synthesizing enzyme GAD 65, and the GABA vesicular transporter The Journal of comparative neurology, 2010; 518(10): 1647-69.
Lee H, Brecha NC Immunocytochemical evidence for SNARE protein-dependent transmitter release from guinea pig horizontal cells Eur J Neurosci, 2010; 31(8): 1388-401.
Lee Helen, Brecha Nicholas C Immunocytochemical evidence for SNARE protein-dependent transmitter release from guinea pig horizontal cells The European journal of neuroscience, 2010; 31(8): 1388-401.
Farrell SR, Raymond ID, Foote M, Brecha NC, Barnes S Modulation of voltage-gated ion channels in rat retinal ganglion cells mediated by somatostatin receptor subtype 4 J Neurophysiol, 2010; 104(3): 1347-54.
Raymond ID, Pool AL, Vila A, Brecha NC A Thy1-CFP DBA/2J mouse line with cyan fluorescent protein expression in retinal ganglion cells Vis Neurosci. 2009 Nov;26(5-6):453-65, 2009; 26(5-6): 453-65.
Raymond Iona D, Pool Angela L, Vila Alejandro, Brecha Nicholas C A Thy1-CFP DBA/2J mouse line with cyan fluorescent protein expression in retinal ganglion cells Visual neuroscience, 2009; 26(5-6): 453-65.
Stella SL Jr, Hu WD, Brecha NC Adenosine suppresses exocytosis from cone terminals of the salamander retina Neuroreport, 2009; 20(10): 923-9.
Stella Salvatore L, Hu Wanda D, Brecha Nicholas C Adenosine suppresses exocytosis from cone terminals of the salamander retina Neuroreport, 2009; 20(10): 923-9.
Guo Chenying, Stella Salvatore L, Hirano Arlene A, Brecha Nicholas C Plasmalemmal and vesicular gamma-aminobutyric acid transporter expression in the developing mouse retina The Journal of comparative neurology, 2009; 512(1): 6-26.
Stella Salvatore L, Li Stefanie, Sabatini Andrea, Vila Alejandro, Brecha Nicholas C Comparison of the ontogeny of the vesicular glutamate transporter 3 (VGLUT3) with VGLUT1 and VGLUT2 in the rat retina Brain research, 2008; 1215(1): 20-9.
Raymond Iona D, Vila Alejandro, Huynh Uyen-Chi N, Brecha Nicholas C Cyan fluorescent protein expression in ganglion and amacrine cells in a thy1-CFP transgenic mouse retina Molecular vision, 2008; 14(1): 1559-74.
Anselmi Nicholas C, Stella Nicholas C, Brecha Nicholas C, Sternini Nicholas C Galanin inhibition of voltage-dependent Ca(2+) influx in rat cultured myenteric neurons is mediated by galanin receptor 1 Journal of neuroscience research, 2008; 512(1): 1107-14.
Hirano Arlene A, Brandstätter Johann Helmut, Vila Alejandro, Brecha Nicholas C Robust syntaxin-4 immunoreactivity in mammalian horizontal cell processes Visual neuroscience, 2008; 24(4): 489-502.
Stella Salvatore L, Hu Wanda D, Vila Alejandro, Brecha Nicholas C Adenosine inhibits voltage-dependent Ca2+ influx in cone photoreceptor terminals of the tiger salamander retina Journal of neuroscience research, 2007; 85(5): 1126-37.
Wang Yuan, Luksch Harald, Brecha Nicholas C, Karten Harvey J Columnar projections from the cholinergic nucleus isthmi to the optic tectum in chicks (Gallus gallus): a possible substrate for synchronizing tectal channels The Journal of comparative neurology, 2006; 494(1): 7-35.
Casini Giovanni, Rickman Dennis W, Brecha Nicholas C Expression of the gamma-aminobutyric acid (GABA) plasma membrane transporter-1 in monkey and human retina Investigative ophthalmology & visual science, 2006; 47(4): 1682-90.
Chang Bo, Heckenlively John R, Bayley Philippa R, Brecha Nicholas C, Davisson Muriel T, Hawes Norm L, Hirano Arlene A, Hurd Ronald E, Ikeda Akihiro, Johnson Britt A, McCall Maureen A, Morgans Catherine W, Nusinowitz Steve, Peachey Neal S, Rice Dennis S, Vessey Kirstan A, Gregg Ronald G The nob2 mouse, a null mutation in Cacna1f: anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses Visual neuroscience, 2006; 23(1): 11-24.
Hirano Arlene A, Brandstätter Johann H, Brecha Nicholas C Cellular distribution and subcellular localization of molecular components of vesicular transmitter release in horizontal cells of rabbit retina The Journal of comparative neurology, 2005; 488(1): 70-81.
D’Angelo I, Brecha NC. Y2 receptor expression and inhibition of voltage-dependent Ca2+ influx into rod bipolar cell terminals, Neuroscience, 2004; 125(4): 1039-49.
Minnis JG, Patierno S, Kohlmeier SE, Brecha NC, Tonini M, Sternini C. Ligand-induced mu opioid receptor and endocytosis and recycling in enteric neurons, Neuroscience, 2003; 119(1): 33-42.
Oh Su-Ja, D’Angelo Iona, Lee Eun-Jin, Chun Myung-Hoon, Brecha Nicholas C Distribution and synaptic connectivity of neuropeptide Y-immunoreactive amacrine cells in the rat retina The Journal of comparative neurology, 2002; 446(3): 219-34.
Casini, G Sabatini, A Catalani, E Willems, D Bosco, L Brecha, NC Expression of the neurokinin 1 receptor in the rabbit retina Neuroscience. , 2002; 115(4): 1309-21.
D’Angelo Iona, Oh Su-Ja, Chun Myung-Hoon, Brecha Nicholas C Localization of neuropeptide Y1 receptor immunoreactivity in the rat retina and the synaptic connectivity of Y1 immunoreactive cells The Journal of comparative neurology, 2002; 454(4): 373-82.
Cueva Juan G, Haverkamp Silke, Reimer Richard J, Edwards Robert, Wässle Heinz, Brecha Nicholas C Vesicular gamma-aminobutyric acid transporter expression in amacrine and horizontal cells The Journal of comparative neurology, 2002; 445(3): 227-37.
Kang, WS Lim, MY Lee, EJ Kim, IB Oh, SJ Brecha, NC Park, CB Chun, MH Light- and electron-microscopic analysis of neuropeptide Y-immunoreactive amacrine cells in the guinea pig retina Cell and tissue research. , 2001; 306(3): 363-71.
Casini, G Brecha, NC Bosco, L Rickman, DW Developmental expression of neurokinin-1 and neurokinin-3 receptors in the rat retina The Journal of comparative neurology. , 2000; 421(2): 275-87.
Melone, M Brecha, NC Sternini, C Evans, C Conti, F Etorphine increases the number of mu-opioid receptor-positive cells in the cerebral cortex Neuroscience. , 2000; 100(3): 439-43.
Sternini, C Brecha, NC Minnis, J D’Agostino, G Balestra, B Fiori, E Tonini, M Role of agonist-dependent receptor internalization in the regulation of mu opioid receptors Neuroscience. , 2000; 98(2): 233-41.
Akopian, A., Johnson, J., Gabriel, R., Brecha, N.C. and P. Witkovsky Somatostatin modulates voltage-gated K+ and Ca2+ currents in rod and cone photoreceptors of the salamander retina, Journal of Neuroscience 20:929-936, 2000; 20: 929-936.
Johnson, J Wu, V Wong, H Walsh, JH Brecha, NC Somatostatin receptor subtype 2A expression in the rat retina Neuroscience. , 1999; 94(3): 675-83.
Johnson, J Wong, H Walsh, JH Brecha, NC Expression of the somatostatin subtype 2A receptor in the rabbit retina The Journal of comparative neurology. , 1998; 393(1): 93-101.
Casini, G Rickman, DW Sternini, C Brecha, NC Neurokinin 1 receptor expression in the rat retina The Journal of comparative neurology. , 1997; 389(3): 496-507.
Johnson, J., Chen, T.K., Rickman, D.W., Evans, C., and Brecha, N.C Multiple g-aminobutyric acid plasma membrane transporters (GAT-1, GAT-2 and GAT-3) in the rat retina, Journal of Comparative Neurology, 1996; 375: 212-224.
Rickman, DW Blanks, JC Brecha, NC Somatostatin-immunoreactive neurons in the adult rabbit retina The Journal of comparative neurology. , 1996; 365(3): 491-503.
Brecha, N., Johnson, J., Kui, R., Anton, B., Keith Jr., D., Evans, C., and Sternini, C. Mu opioid receptor immunoreactivity is expressed in the retina and retinal-recipient nuclei, Analgesia, 1995; 1: 331-334.
Corey, JL Davidson, N Lester, HA Brecha, N Quick, MW Protein kinase C modulates the activity of a cloned gamma-aminobutyric acid transporter expressed in Xenopus oocytes via regulated subcellular redistribution of the transporter The Journal of biological chemistry. , 1994; 269(20): 14759-67.